Nique ID’s in Blue indicate `symptomatic infected’ individuals. (PDF)Table S2 Patient demographics and pre-challenge se-rology for HAI titers to challenge viruse (H3N2). Unique ID’s in Blue indicate `symptomatic infected’ individuals. (PDF)Table SComplete subject list for both H1N1 and H3N2 viral challenge trials, with total symptom scores and clinical/virologic classifications. (PDF)Table S4 Comparison of the top 50 genes from the discriminative factors derived from H1N1 and H3N2 challenge trials, ranked by order of individual contribution to the strength of the Factor (buy AKT inhibitor 2 highest contributors at the top). (PDF)Host Genomic Signatures Detect H1N1 InfectionMethods S1 Additional material defining the statisticalAuthor ContributionsConceived and designed the experiments: CWW GSG TV LC RL-W AGG. Performed the experiments: CWW MTM BN JV RL-W AGG SG ER. Analyzed the data: CWW MTM MC AKZ YH AOH JL LC GSG. Contributed reagents/materials/analysis tools: SFK YH RL-W AGG AOH ER JL LC. Wrote the paper: CWW MTM AKZ GSG.models used are presented. (PDF)The hippocampus is a functionally complex brain area that plays a role in behaviors as diverse as spatial navigation and emotion. Not surprisingly then, it is also structurally complex and there is mounting evidence that distinct subregions along it’s longitudinal axis are subservient to different behaviors. The dorsal (septal) component has been linked to spatial navigation [1?], whereas the ventral (temporal) portion has been associated with emotional responses to arousing stimuli [4,5]. The hippocampus is also particularly sensitive to stress [6], but it appears that the two subregions respond differentially to stressful experiences. For example, acute stressors decrease long term potentiation (LTP) in the dorsal hippocampus, but selectively increase monoamine levels [7] and long-term potentiation in the ventral subregion [8]. Chronic stressors also elicit subregionspecific responses. We have previously shown that adaptive plasticity, such as expression of neuropeptide Y (NPY) and DFosB, were highest in the dorsal subregion following chronic unpredictable stress (CUS), whereas adverse events, including decreased survival of hippocampal progenitor cells, were most severe in theventral subregion [9]. These data suggest that the hippocampus plays a dual role in the response to stress, with the dorsal portion undergoing adaptive plasticity, perhaps to facilitate escape or avoidance of the stressor, and the ventral portion involved in the affective facets of the experience [9]. We reasoned, therefore, that if chronic stress selectively induces adaptive neuroplastic responses in the dorsal hippocampus, spatial navigation would be enhanced by CUS. Accordingly, in the present study, we determined whether CUS enhanced spatial performance in the radial arm water maze (RAWM). The RAWM is a spatial navigation task that is stressful to laboratory rodents because it involves swimming [10]. It is therefore a suitable means by which to place demands on both hippocampal subregions simultaneously. Spatial learning has previously been associated with increased neurotrophin expression and SC1 synaptic remodeling in the hippocampus [11], but whether this varies by subregion has not been investigated. In the present study, we assessed subregion-specific changes in the expression of proteins associated with plasticity, including BDNF, its immature isoform, proBDNF, and postsynaptic density-95 (PSD-95), following a one-day learni.Nique ID’s in Blue indicate `symptomatic infected’ individuals. (PDF)Table S2 Patient demographics and pre-challenge se-rology for HAI titers to challenge viruse (H3N2). Unique ID’s in Blue indicate `symptomatic infected’ individuals. (PDF)Table SComplete subject list for both H1N1 and H3N2 viral challenge trials, with total symptom scores and clinical/virologic classifications. (PDF)Table S4 Comparison of the top 50 genes from the discriminative factors derived from H1N1 and H3N2 challenge trials, ranked by order of individual contribution to the strength of the Factor (highest contributors at the top). (PDF)Host Genomic Signatures Detect H1N1 InfectionMethods S1 Additional material defining the statisticalAuthor ContributionsConceived and designed the experiments: CWW GSG TV LC RL-W AGG. Performed the experiments: CWW MTM BN JV RL-W AGG SG ER. Analyzed the data: CWW MTM MC AKZ YH AOH JL LC GSG. Contributed reagents/materials/analysis tools: SFK YH RL-W AGG AOH ER JL LC. Wrote the paper: CWW MTM AKZ GSG.models used are presented. (PDF)The hippocampus is a functionally complex brain area that plays a role in behaviors as diverse as spatial navigation and emotion. Not surprisingly then, it is also structurally complex and there is mounting evidence that distinct subregions along it’s longitudinal axis are subservient to different behaviors. The dorsal (septal) component has been linked to spatial navigation [1?], whereas the ventral (temporal) portion has been associated with emotional responses to arousing stimuli [4,5]. The hippocampus is also particularly sensitive to stress [6], but it appears that the two subregions respond differentially to stressful experiences. For example, acute stressors decrease long term potentiation (LTP) in the dorsal hippocampus, but selectively increase monoamine levels [7] and long-term potentiation in the ventral subregion [8]. Chronic stressors also elicit subregionspecific responses. We have previously shown that adaptive plasticity, such as expression of neuropeptide Y (NPY) and DFosB, were highest in the dorsal subregion following chronic unpredictable stress (CUS), whereas adverse events, including decreased survival of hippocampal progenitor cells, were most severe in theventral subregion [9]. These data suggest that the hippocampus plays a dual role in the response to stress, with the dorsal portion undergoing adaptive plasticity, perhaps to facilitate escape or avoidance of the stressor, and the ventral portion involved in the affective facets of the experience [9]. We reasoned, therefore, that if chronic stress selectively induces adaptive neuroplastic responses in the dorsal hippocampus, spatial navigation would be enhanced by CUS. Accordingly, in the present study, we determined whether CUS enhanced spatial performance in the radial arm water maze (RAWM). The RAWM is a spatial navigation task that is stressful to laboratory rodents because it involves swimming [10]. It is therefore a suitable means by which to place demands on both hippocampal subregions simultaneously. Spatial learning has previously been associated with increased neurotrophin expression and synaptic remodeling in the hippocampus [11], but whether this varies by subregion has not been investigated. In the present study, we assessed subregion-specific changes in the expression of proteins associated with plasticity, including BDNF, its immature isoform, proBDNF, and postsynaptic density-95 (PSD-95), following a one-day learni.